OBJECTIVES/GOALS: The purpose of this 4-phase exploratory study is to create a human-centered protocol for a new program, CAPABLE-FAMILY, to address older adults with physical disability and dementia and their caregivers. METHODS/STUDY POPULATION: The Szanton-Gill Resilience Model, Verbrugge & Jett Disablement, and Life Span Theory of Control are theoretical frameworks guiding this study. Phase 1. Using qualitative research (n = 10 dyads) methods (ex. Photovoice) we seek to understand the context for older adults with dementia regarding disability. Phase 2. Using synthesis/ideation (n = 10 dyads) tools (ex. Journey Maps) we will synthesize the qualitative research during group ideation sessions with stakeholders. Phase 3. Using prototype testing (n = 3 dyads) methods (ex. Semantic Differentials, Storyboards), we will build the most promising prototypes. Phase 4. Using an open-label pilot (n = 3 dyads), we will test the interventions. RESULTS/ANTICIPATED RESULTS: We will assess disability (ADL, IADL), environmental changes pain, depression, polypharmacy, provider communication needs, and caregiver burden. We will interview the dyads and multiple CAPABLE Registered Nurses (RN), Occupational Therapists (OT), and Handymen (HM) about their prior experiences and perceptions of the pilot. CFQ, MocA, pain (BPI), and ZBI will be measured pre/post RN, OT, HM visit. While there are evidence-based programs to separately address cognitive impairment and physical disability, we anticipate this is the first study to develop a community-based goal-directed, human-centered approach for the maintenance of physical function for persons with dementia in the home. DISCUSSION/SIGNIFICANCE OF IMPACT: Persons with more cognitive impairment did not improve as much as those with less cognitive impairment in the original CAPABLE study, an evidenced based program which reduced disability. This suggests the need to adapt CAPABLE to reduce the burden of disability in persons with Alzheimer’s dementia. CONFLICT OF INTEREST DESCRIPTION: None

OBJECTIVES/GOALS: LSD1 is a histone demethylase important in GBM regulation. Our goal is to design a therapeutic strategy for LSD1 inhibitors to meet clinical needs in GBM. Despite the abundance of LSD1 inhibitors, resistance emerges in GBM mouse models. We aim to understand the relevance of proliferative signaling pathways, such as MAPK, in LSD1 inhibitor resistance. METHODS/STUDY POPULATION: Following LSD1 knockdown in GBM cells, we determined differentially expressed genes using RNA-seq and gene set enrichment analysis (GSEA). Kinase signaling processes enriched for LSD1 expression were identified. Utilizing western blot, we assessed LSD1’s impact on MAPK signaling in patient-derived GBM stem cells (GSCs) and pediatric high-grade glioma cell models. Pharmacological evaluation of LSD1 involved five inhibitor candidates. Additionally, we explored LSD1 inhibition in combination with brain penetrant kinase inhibitors, osimertinib and ulixertinib, directed against the epidermal growth factor receptor (EGFR) and MAPK, respectively. The treatment combinations were assessed at multiple concentrations and analyzed using SynergyFinder. RESULTS/ANTICIPATED RESULTS: Pharmacological LSD1 inhibition after 24 hours induced increased phosphorylated ERK1/2 across multiple glioma cell lines. Concurrent LSD1 and EGFR/MAPK inhibition demonstrated improvedin vitro efficacy compared to individual agents. Notably, the combination of Iadademstat (ORY-1001) and osimertinib demonstrated the highest synergy score of 37.2 using the bliss synergy model in the GSC17s. Furthermore, 11 out of the 12 combination treatments tested had a synergistic relationship, with bliss synergy scores greater than 10. DISCUSSION/SIGNIFICANCE: Our study addresses the pressing need for novel therapeutic strategies in GBM. We leveraged pharmacological tools of LSD1 inhibition to determine how they could be used most effectively, revealing kinase inhibition as a promising strategy with demonstrated in vitro efficacy. Future efforts will focus on validating these findingsin vivo.

OBJECTIVES/GOALS: The SC CTSI Quality by Design (QbD) program aims to improve the execution of clinical research studies identifying and addressing possible issues before implementation. The program’s overall goal is to optimize operational design to achieve an 80% on-time completion rate. METHODS/STUDY POPULATION: Adapted from the Clinical Trials Transformation Initiative, our QbD program applies principles of quality management, project management, and team science to SC CTSI-funded studies. The process begins with a Design Studio for systematic review of critical-to-quality factors and a discussion of risks and mitigation plans. Studio attendees generally include the research team, SC CTSI faculty, and at least one community member. Outcomes include mitigation plans, a study project plan, and continued support from the project-tailored advisory board. We will iteratively evaluate satisfaction, quality improvement, and study completion rates. RESULTS/ANTICIPATED RESULTS: In an evaluation of the pilot phase, QbD participants responded that careful planning and expert input added value to their studies. The QbD process improved the quality of their studies, and all participants plan to apply QbD tools and resources to future studies. Beyond quality improvement, other anticipated outcomes include higher on-time study completion rates and uptake of QbD resources by other research teams. We also plan to assess the comparative benefit of QbD by study type. DISCUSSION/SIGNIFICANCE: Broader application of the CTSI QbD program has the potential for widespread benefit on research processes and outcomes. Studies implemented with minimal avoidable errors are more likely to complete on time, helping ensure efficient use of valuable resources and participant time.

ABSTRACT IMPACT: Despite its importance in systemic diseases such as diabetes, the eye is notably difficult to examine for non-specialists; this study introduces a fully automated approach for eye disease screening, coupling a deep learning algorithm with a robotically-aligned optical coherence tomography system to improve eye care in non-ophthalmology settings. OBJECTIVES/GOALS: This study aims to develop and test a deep learning (DL) method to classify images acquired from a robotically-aligned optical coherence tomography (OCT) system as normal vs. abnormal. The long-term goal of our study is to integrate artificial intelligence and robotic eye imaging to fully automate eye disease screening in diverse clinical settings. METHODS/STUDY POPULATION: Between August and October 2020, patients seen at the Duke Eye Center and healthy volunteers (age ≥18) were imaged with a custom, robotically-aligned OCT (RAOCT) system following routine eye exam. Using transfer learning, we adapted a preexisting convolutional neural network to train a DL algorithm to classify OCT images as normal vs. abnormal. The model was trained and validated on two publicly available OCT datasets and two of our own RAOCT volumes. For external testing, the top-performing model based on validation was applied to a representative averaged B-scan from each of the remaining RAOCT volumes. The model’s performance was evaluated against a reference standard of clinical diagnoses by retina specialists. Saliency maps were created to visualize the areas contributing most to the model predictions. RESULTS/ANTICIPATED RESULTS: The training and validation datasets included 87,697 OCT images, of which 59,743 were abnormal. The top-performing DL model had a training accuracy of 96% and a validation accuracy of 99%. For external testing, 43 eyes of 27 subjects were imaged with the robotically-aligned OCT system. Compared to clinical diagnoses, the model correctly labeled 18 out of 22 normal averaged B-scans and 18 out of 21 abnormal averaged B-scans. Overall, in the testing set, the model had an AUC for the detection of pathology of 0.92, an accuracy of 84%, a sensitivity of 86%, and a specificity of 82%. For the correctly predicted scans, saliency maps identified the areas contributing most to the DL algorithm’s predictions, which matched the regions of greatest clinical importance. DISCUSSION/SIGNIFICANCE OF FINDINGS: This is the first study to develop and apply a DL model to images acquired from a self-aligning OCT system, demonstrating the potential of integrating DL and robotic eye imaging to automate eye disease screening. We are working to translate this technology for use in emergency departments and primary care, where it will have the greatest impact.

OBJECTIVES/GOALS: In 2020 the Georgia CTSA Clinical Research Center site at Emory University developed a highly trained, credentialed research coordinator pool with a goal to expand the pool to include clinical research coordinators from our partner institutions with the ability to work across institutional barriers in support of Georgia CTSA investigators. METHODS/STUDY POPULATION: Fall 2022, an Emory Investigator requested Georgia CTSA Biorepository samples with supporting clinical data for a NIH funded study. This provided a pilot opportunity to utilize clinical research nursing support offered by the UGA Clinical and Translational Research Unit (CTRU). De-identified samples were collected from our Biorepository while Emory’s coordinators and lab collaborated with UGA’s nursing support for data collection. Our obstacle for cross-institutional support was access to Emory Healthcare (EHC) medical records that would be needed by the UGA nurses, but partnerships created with the Georgia CTSA allowed us to overcome this, granting access to the electronic medical records (EMR) needed to complete the study. RESULTS/ANTICIPATED RESULTS: As expected, the process of credentialing and gaining access to the EHC EMR for the UGA team was the most time-consuming in the development of the pool. Discussions began in June 2021 to determine needs to allow the UGA research nurses to support the Emory coordinator pool. Requirements included acquiring an EHC network ID, completion of required Emory research training, letters of support from the Georgia CTSA outlining the collaboration between institutions, and a credentialing application. All steps were completed in May 2022 and the team began to identify studies that could benefit from this collaboration. Given that all credentialing and access needs were in place, the team was able to initiate the study and complete all study requirements, from sample identification to data collection and clean up, in five weeks. DISCUSSION/SIGNIFICANCE: Workforce shortages of experienced clinical research coordinators make it imperative to overcome barriers presented by institutional rules in order to efficiently utilize available resources to conduct high quality research. The CTSAs provide the perfect opportunity for partner institutions to develop processes to allow support across sites.

OBJECTIVES/SPECIFIC AIMS: (1) To define and describe a cohort of patients aged ≥65 years with incident HL from SEER-Medicare data. (2) To identify patient, disease, and system-level factors associated with initial treatment for HL. METHODS/STUDY POPULATION: This retrospective cohort study utilized SEER-Medicare data from 1999-2014. Patients with incident classical HL were identified using SEER registry histology groupings. The cohort was restricted to those with Medicare Part A and B fee-for-service for 3 months prior to and 1 year after diagnosis (or until date of death) in order to fully capture claims for outpatient chemotherapy. Patients were excluded for the following reasons: missing month of HL diagnosis; unknown diagnostic confirmation; reporting from autopsy or death certificate; or another cancer diagnosis +/− 2 years of the HL diagnosis. Demographic and disease characteristics were defined based on SEER registry data. Broad treatment categories were defined using SEER data, while detailed treatment categories will be defined based on Medicare claims. Length of follow-up was defined as the number of months until the earliest of the following: death; end of continuous Medicare Part A and B fee-for-service enrollment; or the end of the available data (12/31/2014). Demographic, disease, and preliminary treatment characteristics were described for the cohort. Future analyses will explore patient and disease factors, including comorbidities and an estimate of frailty, as well as system-level factors associated with initial treatment of HL. RESULTS/ANTICIPATED RESULTS: We identified 2909 patients meeting eligibility for the cohort. The median length of follow-up was 22 months (Q1=5, Q3=62). Median age was 75.9 years (Q1=70, Q3=81), 49.6% were female, and 82.6% were non-Hispanic/White. Only 11.5% of patients were in rural or non-urban areas. 13.8% of patients were dual eligible for both Medicare and Medicaid. Nodular sclerosis was the most common histology (35.2%), followed by mixed cellularity (21.1%); 36.5% had histology that was not otherwise specified. Patients were evenly distributed across Ann Arbor Stage (21.8% with I; 22.3% with II; 25.8% with III; 24.2% with IV; 6% unknown). B symptoms were present in 35.2% of patients, absent in 39.6%, and unknown in 25.2%. Neither tumor bulk nor international prognostic score were available via SEER registry data. According to SEER registry data, most patients received some treatment for their HL (81.9%) and 75% of those patients initiated treatment within one month of diagnosis. 72% of patients died with median time to death of 9 months (Q1=3, Q3=43). DISCUSSION/SIGNIFICANCE OF IMPACT: We successfully identified and described a cohort of 2909 older patients with incident HL from the SEER-Medicare data. This provides a unique opportunity to study this cohort in a large, representative dataset with nearly 15 years of follow up. Future analysis will help us to better understand treatment patterns of HL in older patients and factors associated with treatment. These results can then be used to help improve care decisions and clinical outcomes.

OBJECTIVES/GOALS: Motivations and hesitations about participating in genetic research among those at risk of inherited conditions are unclear. We aim to understand perceptions, perspectives, and concerns of these individuals regarding genetic research studies, especially for hard-to-diagnose diseases. METHODS/STUDY POPULATION: Mix method study of 150 Hispanics individuals in Puerto Rico (PR) at risk for in heriting a condition. These individuals, with limited diagnostic data, are attending genetics clinics or invited to a genetics study at the University of Puerto Rico Medical Sciences Campus. Structured surveys and interviews will be conducted. Surveys will gauge general perceptions and feelings toward genetic research, while interviews will provide a deeper understanding of participants’ personal narratives and experiences. All sessions will be recorded, transcribed, and analyzed using NVivo qualitative analysis software. Thematic analysis will be employed to identify recurring themes and sentiments. RESULTS/ANTICIPATED RESULTS: Weanticipatevaried responses: some enthusiastic about genetic research benefits, others having reservations due to privacy, cultural beliefs, or past experiences. A significant portion may express concerns about genetic research’s impact on insurance and potential discrimination. We also expect to uncover systemic challenges that hinder participation among Hispanics living in PR, such as a lack of information or misconceptions about genetic research. This study will overview factors, both encouraging and inhibitory, influencing decisions to join genetic research. Quantitative genetic literacy survey data will undergo descriptive analysis and multivariate logistic regression. DISCUSSION/SIGNIFICANCE: Hispanics in PR exhibit a rich tapestry of genetic variations being a focal point for genetic research. Understanding perceptions is vital among those at risk for inherited conditions. Insights can shape outreach and education strategies, ensuring participants are informed, concerns met, and empowered to make decisions alignined their views.

ABSTRACT IMPACT: Grouping patients with potentially high intensity specialty care needs based on their propensity for healthcare continuity patterns can inform the development of personalized care coordination and care navigation interventions OBJECTIVES/GOALS: To examine variation in healthcare continuity patterns across primary care, mental health care, and specialty care for a patient population with chronic gastrointestinal conditions and a high risk for healthcare utilization. METHODS/STUDY POPULATION: We analyzed data for Veterans Affairs patients with chronic gastrointestinal disease (cirrhosis, inflammatory bowel disease, chronic pancreatitis) whose 1-year hospitalization risk was ≥90th percentile in 2014, and who had a minimum of 4 office visits. To assess continuity, we examined frequency of office visits, number of outpatient providers, and two established continuity of care measures (the usual provider of care index and the Bice-Boxerman continuity of care index) over 12 months. We used latent class analysis to categorize patients into classes based on overall, primary care (PCP)-specific, gastroenterology (GI)-specific, and mental health specific-healthcare continuity patterns. RESULTS/ANTICIPATED RESULTS: The 26,751 Veterans in the analytic cohort had a mean of 13.3 (sd 8.63) office visits and 7.2 (sd 3.83) providers per patient. Patients were classified into five phenotypes: (1) moderate overall use and continuity; (2) low overall continuity of care; (3) high GI- and PCP-specific continuity of care; (4) low overall continuity of care with some mental health use; and (5) high utilization with substantial mental health use. In the subsequent year, 11,259 (42.1%) patients had a hospitalization and 16,167 (60.4%) had an emergency department visit. These groups varied in their sociodemographic and clinical characteristics, and in their risk for hospitalization and emergency department use. DISCUSSION/SIGNIFICANCE OF FINDINGS: Latent class analysis revealed five distinct primary and specialty care utilization patterns. Grouping patients with high intensity specialty care needs based on their propensity for healthcare continuity patterns can inform the development of personalized care navigation interventions.

OBJECTIVES/GOALS: Cervical cancer is the fourth most common cancer among women worldwide, with approximately 570,000 newly diagnosed cases and 311,000 related deaths among women in 2018.In the United States, approximately 13,000 new cases of cervical cancer are diagnosed annually with approximately 4,000 women dying each year from cervical cancer. Nearly all cervical cancer is caused by oncogenic strains of the human papillomavirus (HPV). Prevention strategies to reduce cervical cancer after HPV exposure entail treatment of cervical dysplasia at the premalignant state, specifically low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL), along with the eventual clearance of HPV.The most common treatment for persistent LSIL or HSIL is the loop electrical excisional procedure (LEEP). This procedure is unfortunately not widely available in resource-limited countries and is associated with potential significant morbidities, including decreased fertility, preterm birth, premature rupture of membranes and cervical incompetence. Despite undergoing standard of care treatment, in certain high-risk populations, specifically HIV-infected women, there is a higher rate of premalignant HPV-related cervical disease persistence, progression and recurrence.There is a paramount need for novel nonsurgical treatments to stabilize or treat precancerous lesions of the cervix and to decrease the persistence of HPV infection. Medical treatment with the natural herb curcumin may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Curcumin is a major active component extracted from turmeric with anti-inflammatory, anti-infectious, and anti-cancer properties.Topical intravaginal curcumin has the promise of delivering this drug directly to the site of disease, ensuring adequate concentrations at the site of disease while avoiding systemic side effects. This proposed study will determine if there are higher rates of HPV clearance after curcumin administration among women with and without HIV who have premalignant HPV-related cervical disease, specifically LSIL or recently treated (with a LEEP) HSIL. METHODS/STUDY POPULATION: We are proposing a prospective double-blind randomized control trial to investigate the utility of topical intra-vaginal curcumin in increasing rates of HPV clearance and mitigating the high rates of disease recurrence in women with and without HIV. A sample of approximately 200 women with and without HIV who have biopsy-proven LSIL or recently treated HSIL will be randomized to one of two arms: 2000 mg of curcumin powder in capsules or placebo inserted intravaginally at bedtime once weekly for 20 weeks (excluding the time of menses). Cervical cytology and HPV testing will be performed at baseline and 6 months post-randomization. If a participant has abnormal cytology or a positive high-risk HPV test 6 months post-randomization, they will be scheduled to undergo a colposcopy with biopsies of all suspicious cervical lesions. If biopsy results are HSIL or greater, subjects will be referred back to routine clinical treatment, which may include a LEEP. Clinicians performing the colposcopies and the study participants will be blinded since the placebo has the same appearance as the curcumin capsules. At the end of the study, study participants will be offered the opportunity to participate in 2-3 hour focus groups to discuss acceptability of the product as a treatment for premalignant HPV-related cervical disease until data saturation is achieved. Power and sample size calculations are based on the primary outcome of interest, which is clearance of HPV at 6 months. Basu et al (2013) documented HPV clearance in as many as 80% of subjects with topical curcumin. To account for an expected lower success rate in HIV-infected women, who will also be included in the study, we intend to power our study to determine a more conservative 20% improvement in clearance rate at 6 months with curcumin treatment, assuming an expected clearance rate of HPV in HIV-infected women of 25%. In order to detect a 20% difference of HPV clearance among those treated with intravaginal curcumin vs. placebo at 6 months, about 80 patients per arm would achieve 80% power at the 5% significance level. To account for up to 20% loss to follow-up or discontinuation, the total sample size in each arm would be 100 subjects with a total of approximately 200 subjects enrolled in both arms. RESULTS/ANTICIPATED RESULTS: We are currently in the process of collecting data for this study. We hypothesize that intravaginal curcumin will have a 20% higher rate of HPV clearance at 6 months as compared to placebo. Primary outcome measures will include clearance of HPV at 6 months in curcumin vs. placebo. Secondary outcomes measures will include recurrence of disease by either cytologic or histologic abnormality requiring further surveillance or treatment at 6 months. We also hypothesize that intravaginal curcumin administered once weekly at bedtime for 20 weeks will be safe, acceptable, and well tolerated. This is based off of previous findings from the Phase 1 trial of intravaginal curcumin that we performed. During this Phase 1 trial, we explored daily intravaginal administration of 2000 mg of curcumin to further understand curcumin’s tolerability. Our focus group participants displayed an overwhelming consensus that daily administration affected quality of life, specifically due to the yellow-colored vaginal discharge from the medication. Study participants expressed that once or twice weekly administration was more tolerable and feasible. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. The primary outcome measure will be the proportion of study participants who discontinue treatment for any reason (acceptability) and the proportion of study participants who discontinue treatment due to adverse effects (tolerability). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-surgical treatments that decrease the morbidity and risk of progression of premalignant HPV-related cervical disease are greatly needed, especially in low-resource settings and among women experiencing barriers to care and/or at high risk for disease progression. Medical treatment with the natural herb curcumin is an emerging strategy that may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Several preclinical and clinical studies have shown curcumin’s ability to reduce tumors and precancerous lesions in animal and human cancer cells. Curcumin can suppress the activation of transcription factor NF-κB and the expression and activity of VEGF and p16INK4a, biomarkers known to be elevated in premalignant HPV-related cervical disease.Studies have also shown that curcumin alters HPV-associated molecular pathways in cancer cells, suppressing cervical cancer growth by inhibiting the transcription of oncoproteins HPV16 and HPV18 (designated as E6 and E7) and restoring p53 and retinoblastoma function. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. Our results will generate novel data as to what is an acceptable and well-tolerated dosing regimen of intravaginal curcumin, which would be crucial in designing further curcumin intervention studies. The results of our proposal will explore the effect of intravaginal curcumin as a standalone and adjuvant therapy to a LEEP among women with premalignant HPV-related cervical disease. The potential to not just excise diseased tissue, but to directly augment the clearance of the causative agent HPV, would have profound long-term ramifications in resource-limited settings and among women experiencing barriers to care and/or at high risk for disease progression.

Dyads can be challenging to recruit for research studies, but detailed reporting on strategies employed to recruit adult–adolescent dyads is rare. We describe experiences recruiting adult–youth dyads for a hypertension education intervention comparing recruitment in an emergency department (ED) setting with a school-based community setting. We found more success in recruiting dyads through a school-based model that started with adolescent youth (19 dyads in 7 weeks with < 1 hour recruitment) compared to an ED-based model that started with adults (2 dyads in 17 weeks with 350 hours of recruitment). These findings can benefit future adult–youth dyad recruitment for research studies.

OBJECTIVES/GOALS: Distinguishing tumor tissue from normal brain parenchyma remains a major challenge during the resection of gliomas, leading to the persistence of tumor cells. This study aims to assess the choline kinase alpha-targeting fluorophore JAS239 as a novel fluorescent agent to intraoperatively visualize gliomas in an orthotopic murine model. METHODS/STUDY POPULATION: The human glioblastoma-derived U87 MG-Luc2 cell line will be intracranially implanted in nude mice and tumor growth will be assessed using bioluminescence imaging. After 14 days, the mice will be treated with either antiangiogenic therapy (10 mg/kg bevacizumab, twice/week) or saline (control). Tumor growth will be monitored until 21-28 days after initial implantation, at which point JAS239 (4.0 mg/kg, 90 min before sacrifice) and Evans Blue (4 ml/kg, 60 min before sacrifice) will be administered. The mice will be sacrificed, and their brains will be harvested and sectioned for near-infrared imaging. The brain sections will be processed for histopathologic analysis, allowing for the correlation of observed fluorescence with the distribution of tumor and comparison of signal-to-background ratios. RESULTS/ANTICIPATED RESULTS: JAS239 is an indocyanine-based choline mimetic (excitation 745 nm, emission 775 nm) that has been shown to cross the blood-tumor barrier (BTB) in rodent glioblastoma studies. PET imaging with choline-based radiotracers like 18F-choline has also been shown to delineate both contrast-enhancing tumor (CET) and non-contrast-enhancing tumor (NCET) regions, supporting the hypothesis that JAS239 will be able to visualize heterogeneous glioma tissue in our mouse model. Evans Blue is a passive dye in the visible light spectrum (excitation 620 nm, emission 680 nm) expected to only fluoresce in CET regions due to the disruption of the BTB. JAS239 is expected to fluoresce in both CET and NCET regions, which will be assessed by the fluorescence in mice treated with bevacizumab (expected to renormalize the BTB and model NCETs). DISCUSSION/SIGNIFICANCE: JAS239 may allow for real-time visualization of heterogeneous glioma tissue, which is important because there are no current intraoperative imaging agents for NCETs. Future research and clinical translation of this class of agents may allow surgeons to maximize the safe resection of gliomas, improving progression-free and overall survival rates.

ABSTRACT IMPACT: Our study suggests that maternal e-cigarette use may reduce fetal growth and pose harm to newborns. OBJECTIVES/GOALS: Women are motivated to quit smoking during pregnancy. Many view electronic cigarettes (e-cigarettes) as a safer and healthier alternative to traditional tobacco smoke. We aim to determine the effect of third-trimester e-cigarette use on the risk of infant related outcomes. METHODS/STUDY POPULATION: We conducted a cross-sectional survey study using Pregnancy Risk Assessment Monitoring System (PRAMS). Women who gave live singleton births in 2016-2018 and at states that met response rate threshold criteria were included. Women were classified as never smokers, sole e-cigarette smokers, sole traditional cigarette smokers, and dual-users. Logistic regression was conducted to determine the association between third-trimester cigarette use and preterm birth (<37 weeks), low birth weight (<2,500 grams), and small for gestational age births (SGA, weight lower than the tenth percentile of the population). Analyses were weighted to account for the survey design and non-response. RESULTS/ANTICIPATED RESULTS: 94,539 women (weighted population of 4,765,290) were included. Compared with never smokers, third-trimester sole e-cigarette use increased the odds of preterm birth (Adjusted odds ratio [AOR]: 1.61, 95% confidence interval [CI]: 1.05, 2.48), low birthweight (AOR: 1.49, 95%CI: 1.06, 2.09), and SGA (AOR: 1.19, 95%CI: 0.71, 2.00), sole traditional cigarette use increased the odds of preterm birth (AOR: 1.36, 95%CI: 1.21, 1.52), low birthweight (AOR: 1.90, 95%CI: 1.72, 2.10), and SGA (AOR: 2.28, 95%CI: 2.05, 2.53); and dual use increased the odds of preterm birth (AOR: 1.17, 95%CI: 0.82, 1.67), low birthweight (AOR: 2.16, 95%CI: 1.58, 2.96), and SGA (AOR: 2.67, 95%CI: 1.97, 3.64). DISCUSSION/SIGNIFICANCE OF FINDINGS: E-cigarette use, by itself or in combination with traditional cigarettes, increases the risk of preterm birth, low birthweight, and SGA. Our study suggests that maternal e-cigarette use may reduce fetal growth and pose harm to newborns.

OBJECTIVES/GOALS: The goal of the Hatchery is a new approach to de-risk innovative life science ideas within an entrepreneurial setting. The Hatchery creates value by vetting the initial potential through experimental testing. METHODS/STUDY POPULATION: In this study we took a functioning wet laboratory space that was vacant due to principle investigator movement, and created a pipeline for its use in life science startup formation. A functioning laboratory can remain unoccupied for a notable period with transitions of research leadership. At the same time, a life science startup company who is testing core principles of their technology need wet lab space at an affordable cost. Our solution called the Hatchery provides startup companies a state-of-the-art wet laboratory space, next to a research hospital, for a very short duration of time and minimal fee. This novel approach allows preliminary validation of a technology for initial NIH SBIRs and STTRs funding pathways. RESULTS/ANTICIPATED RESULTS: Initial findings demonstrated the effectiveness of the Hatchery method. Our pilot study included five different life science startups company tenants. Each company was enabled to de-risk technologies and secure a phase 1 SBIR/ STTR funding or resulted in an exit via acquisition. DISCUSSION/SIGNIFICANCE: Entrepreneurship is a growing approach for testing and expanding new research areas. The Hatchery model makes use of existing space and infrastructure, can scale with an entrepreneurial community, and can serve as critical pilot data for a more permanent space commitment.

ABSTRACT IMPACT: Demonstrate applicability of an underutilized method for showing variation that enables public health agencies to respond to the COVID-19 pandemic OBJECTIVES/GOALS: Enacting sensible public policies in the coronavirus disease 2019 (COVID-19) pandemic requires real-time data that civic and public health leaders can easily interpret and act on. This collaboration between a CTSA and a local health department sought a novel use of control charts to provide timely and interpretable data. METHODS/STUDY POPULATION: Healthcare and other industries use control charts to understand the behavior of processes and systems so they can intervene on them. The CTSA science team developed statistical process control charts at the neighborhood level to help illustrate their value for decision-making as the pandemic progresses. This method included accounting for congregate populations (skilled nursing facilities, correctional facilities) to produce data for the general public. RESULTS/ANTICIPATED RESULTS: Patterns in COVID-19 vary over time by neighborhood. Juxtaposing control charts with social characteristics of local areas in a dashboard format provides granularity for decision-makers and data for engaging communities in changing behavior. Annotating time series charts in real time connects events and local knowledge with observed data, which can help authorities and people to learn and act based on variations displayed by the control charts about disease outbreaks and cases. School districts are among those that could benefit from control charts with information about the school community and how COVID-19 spread is occurring. DISCUSSION/SIGNIFICANCE OF FINDINGS: Control charts have rarely been used in public health despite their ease of use and interpretability. This study demonstrates a novel approach to providing timely, accurate data that can support real-time decision-making of government and public health as well as school districts, businesses, and others.

OBJECTIVES/GOALS: Evaluate effectiveness of participant recruitment service to improve study enrollment through customer feedback surveys and recruitment data obtained by research teams utilizing services. Use survey information to conduct gap analysis of additional support needed for participant recruitment. METHODS/STUDY POPULATION: Participant enrollment is often cited as one of the most challenging aspects of clinical research. In 2021, the Indiana CTSI used project management techniques to design and pilot a Team Science approach for providing participant recruitment support to clinical research teams. This service called the Indiana CTSI Recruitment Concierge Service (RCS) is comprised of recruitment, community engagement, social media, communications, and project management expertise. Additional experts are chosen to participate based on the study needs (regulatory, population insight, informatics, clinical services, etc.) RCS customers are comprised of study teams from a variety of areas and research experience. These customers are sent surveys to evaluate the support they received and provide suggestions for improvement. RESULTS/ANTICIPATED RESULTS: The RCS assisted 72 study teams in 2021 and 85 (as of November) in 2022. These studies were referred via word of mouth as no advertising of the service had been done to date. All customers were provided a study specific consultation with recommendations of services and resources that would assist their study. Some services recommended were: local study listing and volunteer registry (All IN for Health), digital marketing support, materials design expertise, community engagement and healthcare patient recruitment guidance. The overall feedback from RCS customers has been positive with most teams indicating the support improved their study recruitment and/or engagement plan. RCS will use information obtained to develop a strategy for prioritizing services due to the overwhelming number of requests received. DISCUSSION/SIGNIFICANCE: Using project management techniques and a Team Science approach, the Indiana CTSI was able to develop a comprehensive participant recruitment service that integrates clinical research operations, community engagement, and informatics expertise to design study specific recruitment plans and coordination of services.

OBJECTIVES/GOALS: This study has two primary aims: 1) evaluate points of success and failure in connecting hepatitis C virus (HCV) positive homeless patients to care following a preliminary positive rapid HCV test result, and 2) describe the barriers cited by patients who drop out at each step in the care continuum. METHODS/STUDY POPULATION: A retrospective longitudinal analysis of adult (18 years or older) homeless individuals accessing shelter at six homeless shelters in New Orleans, LA was conducted. Every patient who came through a testing site received a survey collecting information on demographics, barriers to healthcare, and recent utilization of health services. A retrospective chart review of hospital and homeless clinic medical records was used to track patient linkage to care and their progress through the HCV care continuum. We defined successful linkage to care as attendance at the first scheduled follow-up appointment for treatment with a primary care physician. RESULTS/ANTICIPATED RESULTS: A total of 1719 unique patients were identified from August 2016 through August 2019 which included 36% self-identified as African American/Black, 55% identified as White and 8% identified as mixed-race or other. A total of 24% of individuals reported no insurance coverage while 66% of patients reported having insurance. Overall, 85 patients reported they experienced no barriers to healthcare. Of those who reported barriers, 44% reported trouble with finances or insurance, 22% transportation, 18% personal drug use, 9% personal alcohol use, and 7% reported a distrust of healthcare providers or the system. Other barriers included long wait times, distance, and recent incarceration. DISCUSSION/SIGNIFICANCE OF IMPACT: Although screening for HCV is readily available, barriers exist which prevent diagnosis and treatment. We implemented a HCV testing and linkage-to-care program between local homeless shelters and health centers in New Orleans in an effort to reduce HCV-related morbidity and mortality.

OBJECTIVES/GOALS: Cognitive dysfunction and/or depressionfollowing ischemic stroke results in loss of independence in daily functioning. The objective of this work is to assess neural correlates of post-stroke cognitive deficits and the effect of left frontal transcranial electrical stimulation on cognitive control and associated brain rhythms. METHODS/STUDY POPULATION: We recorded midfrontal scalp EEG from 15 healthy and 13 participants with stroke while they performed a multi-source interference task (MSIT). The stroke cohort also performed additional MSIT sessions where they received active and sham transcranial direct current stimulation (tDCS) on the left prefrontal cortex (PFC). The EEG was pre-processed to get rid of eye movement and other channel noise artifacts and filtered to retain 0.5-55 Hz components. A Morlet wavelet was used to estimate power in theta (4-8 Hz), alpha (8-15 Hz) and gamma (35-50 Hz) frequency bands over a period of 2 seconds following MSIT image presentation. A generalized linear mixed effects model was used to find effect of group on behavior and EEG oscillations. A GLME was also used to find effects of active tDCS on behavior and EEG. RESULTS/ANTICIPATED RESULTS: We found Group (healthy v stroke) as a significant predictor of both response time (behavior) and conflict evoked theta power in the frontal channels (F1-Fz, F2-Fz). We also found that active tDCS significantly improved MSIT performance as compared to sham, after accounting for cognitive load. Active tDCS also induced low frequency oscillations in frontal EEG channels compared to sham. Preliminary results indicate that mid-frontal theta oscillations are a potential neural correlate of post-stroke cognitive deficit and tDCS of the left PFC might be a promising therapeutic intervention to ameliorate this. DISCUSSION/SIGNIFICANCE: Current therapeutic approaches often do not alleviate post stroke executive dysfunction, hence a better understanding of the brain network changes underlying such deficit can elucidate neural correlates of post stroke cognitive deficit to inform the development of neuromodulation interventions.